In order to discriminate between a hereditary (about 2–3% of all CRC) or a sporadic event (about 15%), tumors with immunohistochemical loss of MLH1 should then be further investigated for MLH1 promoter hypermethylation and targeted BRAF (V600E hotspot mutation) testing to decide on further (germ line) genetic testing. Here, MLH1 is linked to colorectal carcinoma.